The workings of the amyloid diseases

Vittorio Bellotti, Mario Nuvolone, Sofia Giorgetti, Laura Obici, Giovanni Palladini, Paola Russo, Francesca Lavatelli, Vittorio Perfetti, Giampaolo Merlini

Research output: Contribution to journalArticlepeer-review


The amyloidoses constitute a large group of diseases caused by an alteration in the conformation and metabolism of several globular proteins which, under particular conditions, deposit in tissues as insoluble fibrillar aggregates. To date, at least 24 different proteins have been recognized as causative agents of amyloid diseases. Despite a high heterogeneity in amino acid sequence, three-dimensional structure, and biological function, all amyloidogenic proteins share a reduced folding stability, a strong propensity to acquire more than one conformation, and the capacity to form almost indistinguishable amyloid fibrils. In some cases, the generation of an aggregation-prone state can be triggered or enhanced by the occurrence of mutations, a proteolytic cleavage, or a seeding process. The interaction between the amyloidogenic precursor, some common components of amyloid deposits, and the extra-cellular environment also plays a role in fibrillogenesis and in particular in the organ tropism of amyloid deposition. The process of amyloid fibril formation exerts a cytotoxic effect, resulting in tissue damage and organ dysfunction. Prefibrillar aggregates are thought to have an active part in this process. Due to the pathogenic complexity of amyloid diseases, the integration of several therapeutic interventions involving different critical levels of the amyloidogenic cascade is envisaged.

Original languageEnglish
Pages (from-to)200-207
Number of pages8
JournalAnnals of Medicine
Issue number3
Publication statusPublished - 2007


  • Amyloid diseases
  • Organ failure
  • Protein misfolding
  • Tissue damage

ASJC Scopus subject areas

  • Medicine(all)


Dive into the research topics of 'The workings of the amyloid diseases'. Together they form a unique fingerprint.

Cite this